Functional mapping of transsynaptic effects of local manipulation of inhibition in gerbil auditory cortex

Cortical networks are under the tonic influence of inhibition which is main ly mediated by GABA. The state of inhibition of small neuronal populations in the auditory cortex (AC) field AI of gerbils was altered by local microi njection of GABA, of the GABA(A)-receptor agonist 4-piperidine-sulfonic aci d (PIS) and the GABA(A)-receptor antagonists bicuculline methiodide (BMI) a nd SR-95531. In order to elucidate direct and transsynaptic effects of the alterations of inhibition produced by these substances we used the 2-fluoro -2-deoxy-D-[C-14(U)] glucose (FDG) mapping method. The injection of GABA (1 0 mM) caused no significant changes in FDG labeling but P4S caused a marked decrease of local FDG uptake in a small region surrounding the injection s ite but in no other region. The injection of the GABA(A)-receptor antagonis ts caused massive increases of FDG uptake within the entire ipsilateral AC, whereas the contralateral AC was not significantly affected in spite of pr ominent callosal connections. However, disinhibited excitatory output from the ipsilateral AC is suggested by a strong increase in FDG labeling of the corticothalamic fiber tract and ipsilateral structures like medial genicul ate nucleus, caudal striatum, and lateral amygdaloid nucleus and a structur e at the caudoventral margin of the thalamic reticular nucleus, presumably the subgeniculate nucleus, a structure with hitherto unknown connections an d function. No alteration of FDG uptake could be detected in the inferior c olliculus, another main descending target structure of the AC. In summary, the effects resulting from microinjection of GABA(A)-receptor antagonists r eflect a differential influence of the AC on its anatomically connected tar get regions. The findings demonstrate the potential of the method of focal application of neuroactive substances in combination with the FDG technique for mapping their transsynaptic influences which are hard to derive from a natomical tracing studies alone. (C) 1999 Elsevier Science B.V. All rights reserved.